ArticleCirculation research2012
MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Connexin 43 C-terminus directly inhibits the hyperphosphorylation of Akt/ERK through protein-protein interactions in glioblastoma.Cancer science · 2018Pooled it
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- Connexin 43 in Pathophysiology of Cardiac Diseases: From Molecular Mechanisms to Therapeutic Strategies.Physiological research · 2025Review
- Bridging the gap: connexin 43 at the frontline of endothelial repair.American journal of physiology. Heart and circulatory physiology · 2025Article
- Injury-induced connexin 43 expression regulates endothelial wound healing.American journal of physiology. Heart and circulatory physiology · 2025Article
- Pseudorabies virus infection triggers pUL46-mediated phosphorylation of connexin-43 and closure of gap junctions to promote intercellular virus spread.PLoS pathogens · 2025Article
- Endothelial-adipocyte Cx43 Mediated Gap Junctions Can Regulate Adiposity.Function (Oxford, England) · 2024Article
- Pannexin-3 stabilizes the transcription factor Bcl6 in a channel-independent manner to protect against vascular oxidative stress.Science signaling · 2024Article
- Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer.Cancers · 2024Article
- The conducted vasomotor response and the principles of electrical communication in resistance arteries.Physiological reviews · 2024Review
- Integrative Analysis of N6-methyladenosine RNA modifications related genes and their Influences on Immunoreaction or fibrosis in myocardial infarction.International journal of medical sciences · 2024Article
- The roles of connexins and gap junctions in the progression of cancer.Cell communication and signaling : CCS · 2023Review
- Connexin 43 across the Vasculature: Gap Junctions and Beyond.Journal of vascular research · 2023Review
- Red blood cell eNOS is cardioprotective in acute myocardial infarction.Redox biology · 2022Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.Frontiers in cardiovascular medicine · 2022Review
- New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling.International journal of molecular sciences · 2021Review
- Pathogenesis and Clinical Significance of In-Stent Restenosis in Patients with Diabetes.International journal of environmental research and public health · 2021Review
- New Insights on the Role of Connexins and Gap Junctions Channels in Adipose Tissue and Obesity.International journal of molecular sciences · 2021Review
- Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleDedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.
objectiveTo investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation. METHODS AND
resultsWe show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE(-/-)) mice and in C57Bl/6 mice treated with platelet-derived growth factor-BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43(CT)) and produced null phosphorylation Ser>Ala (Cx43(MK4A)/Cx43(CTMK4A)) and phospho-mimetic Ser>Asp (Cx43(MK4D)/Cx43(CTMK4D)) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43(+/+)) and Cx43 null (Cx43(-/-)) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.
conclusionsWe identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.